Malarial pigment hemozoin and the innate inflammatory response

Our plain-English summary of Malarial pigment hemozoin and the innate inflammatory response, by M. Olivier, K. Van Den Ham, M.T. Shio, et al (Frontiers in Immunology, 2014).

The study

• Authors: M. Olivier, K. Van Den Ham, M.T. Shio, F.A. Kassa, S. Fougeray
• Journal: Frontiers in Immunology
• Published: 2014;5:25
• Type of article: Review
• Cited by: 113 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malaria is a deadly infectious disease caused by the intraerythrocytic protozoan parasite Plasmodium. The four species of Plasmodium known to affect humans all produce an inorganic crystal called hemozoin (HZ) during the heme detoxification process. HZ is released from the food vacuole into circulation during erythrocyte lysis, while the released parasites further infect additional naive red blood cells. Once in circulation, HZ is rapidly taken up by circulating monocytes and tissue macrophages, inducing the production of pro-inflammatory mediators, such as interleukin-1β (IL-1β). Over the last few years, it has been reported that HZ, similar to uric acid crystals, asbestos, and silica, is able to trigger IL-1β production via the activation of the NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome complex. Additionally, recent findings have shown that host factors, such as fibrinogen, have the ability to adhere to free HZ and modify its capacity to activate host immune cells. Although much has been discovered regarding NLRP3 inflammasome induction, the mechanism through which this intracellular multimolecular complex is activated remains unclear. In the present review, the most recent discoveries regarding the capacity of HZ to trigger this innate immune complex as well as the impact of HZ on several other inflammatory signaling pathways will be discussed.

In plain English

This article is a review, not an original study, and its subject is malaria, not asbestos. The authors reviewed published research on hemozoin, a crystal made by malaria parasites as they digest hemoglobin, and on how it triggers inflammation. Asbestos appears only as a comparison. The authors noted reports that hemozoin, like uric acid crystals, asbestos and silica, can trigger the inflammatory signal IL-1β through an immune-cell complex called the NLRP3 inflammasome. They also described differences. In their account, asbestos, silica and MSU crystals disrupt the cell compartment that holds engulfed particles and are highly damaging to cells. Hemozoin, by contrast, can stay inside host cells for several days to weeks without discernably affecting their viability, and is markedly smaller and fully engulfed. The authors concluded that hemozoin is a powerful modulator of the innate immune response. They noted contradicting results between studies, which they attributed partly to differences in cell types, incubation times and crystal quality. The review presents no data on people exposed to asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of published research on the malarial pigment hemozoin and inflammation
• Who was studied: No study population of its own. The review covers earlier laboratory studies (human and mouse immune cells, mice) and clinical observations on hemozoin in malaria.
• Exposure: Hemozoin, a crystal produced by malaria parasites from hemoglobin. Asbestos is mentioned only as a comparison crystal that, like hemozoin, has been reported to trigger IL-1β through the NLRP3 inflammasome. No fiber type is named.
• Main results:
  • The review describes studies, including the authors' own laboratory's, reporting that hemozoin-induced IL-1β production and neutrophil recruitment depended on the NLRP3 inflammasome.
  • According to the review, hemozoin does not appear to disrupt the phagolysosome (the cell compartment holding engulfed material). It stays in vacuoles surrounded by LAMP-1. The review contrasts this with asbestos and silica, for which cathepsin B is generally found in culture supernatant.
  • The authors stated that inorganic crystals such as asbestos, silica and MSU disrupt phagolysosome integrity and are highly apoptotic and disruptive to cell integrity.
  • By contrast, the authors stated that hemozoin can remain in host cells for several days to weeks without discernably affecting phagocyte viability.
  • The authors stated that hemozoin is markedly smaller than asbestos, silica and MSU crystals and is fully engulfed by host cells.
  • The authors reported that their own earlier study found Lyn/Syk kinases to be upstream signaling partners in hemozoin's activation of the NLRP3 inflammasome.
• The authors' conclusion: The authors concluded that hemozoin is a powerful modulator of the innate immune response, with the potential to be detrimental or beneficial to the host depending on the stage of infection.
• Limitations the authors state:
  • The authors noted contradicting results across studies on how hemozoin modulates the immune response.
  • The authors attributed these differences partly to the cell types and incubation times used, and most prominently to the quality of the hemozoin crystals.
  • The authors stated that the cellular receptors recognizing hemozoin remain unidentified.
  • The authors stated that the protection seen in NLRP3-deficient mice cannot be attributed solely to hemozoin.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage.

Related studies

• Immunopathological effects of malaria pigment or hemozoin and other crystals — A. Tyberghein, K. Deroost, et al. (2014)
• Phagocytosis of hemozoin (native and synthetic malaria pigment), and Plasmodium falciparum intraerythrocyte-stage parasites by human and mouse phagocytes — P. Olliaro, L. Lombardi, et al. (2000)
• Cigarette smoke represses the innate immune response to asbestos — G.F. Morris, S. Danchuk, et al. (2015)
• The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells — F.A. Murphy, A. Schinwald, et al. (2012)
• Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma — A. Napolitano, L. Pellegrini, et al. (2016)
• SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro — E. Herzog, H.J. Byrne, et al. (2009)

Browse more research in Frontiers in Immunology, or return to medical research.